Lung Cancer (LC), the dominant cancer killer in the industrialized world, causes one death every 4 minutes in the U.S. Local hyperthermia is used adjunctively with radiation and chemotherapy to augment the efficacy of treatment in other cancers, yet no hyperthermia modality effectively provides localized deep heating in the lung. Comprehensive new approaches to lung hyperthermia are being developed based on filling the lung with non-toxic liquid(s) of unique biological properties and lung-function compatibility. The liquids, termed "perfluorocarbons" (PFC), can be used 1) to directly heat lung via convective heat transfer, or 2) may provide an acoustic medium for ultrasound heating. Simultaneously, the liquids can augment radiotherapy by hyperoxygenating the lung, or can provide chemotherapy concentrated in the lung. Additionally, lung tumors along the major bronchial airways (the site for 3/4 of primary LC's), can be heated via minimally invasive intracavitary ultrasound applicators mechanically resembling bronchoscopes. The Phase I research demonstrated in vivo the feasibility of heating lungs via both the convention and ultrasound modalities, and experimentally showed that small intracavitary applicators are achievable. Auspiciously, the first U.S. clinical studies involving PFC fluids for ventilation also began during the Phase I period.